Identification of a novel CACNA1A mutation in a Chinese family with autosomal recessive progressive myoclonic epilepsy.
Identification of a novel CACNA1A mutation in a Chinese family with autosomal recessive progressive myoclonic epilepsy.
复制标题
一个常染色体隐性遗传进行性肌阵挛癫痫中国家系中新 CACNAIA 突变的鉴定
DOI：
10.2147/ndt.s145774
复制
发表时间：
2017
影响因子：
3.2
通讯作者：
Cui L
中科院分区：
文献类型：
--
作者：
Lv Y;Wang Z;Liu C;Cui L
进行性肌阵挛性癫痫（PME）是一种异质性神经退行性疾病，常表现为难治性癫痫发作和神经功能恶化。PME预后差，因此早期诊断PME至关重要。本研究的目的是在一个中国PME家系中发现新的致病基因，为今后的研究提供帮助。招募了一个三代血缘的中国汉族PME家系。通过外显子组测序技术鉴定了一个新的纯合变异体，并通过桑格测序和功能预测进行了验证。在PME家族中鉴定出CACNA 1A中的一种新的纯合变体c.6975_6976insCAG。编码钙通道Cav2.1的α-1A亚基的新变体在中国家庭的两个兄弟姐妹中发现，并且在50名正常对照中不存在。我们的研究表明，纯合的c.6975_6976insCAG可能是PME的致病突变。作为一种分子诊断策略，我们的研究探索了PME的突变基因谱，并为遗传咨询提供了重要的预测。
Progressive myoclonic epilepsy (PME) is a heterogeneous neurodegenerative disorder, which is commonly manifested with refractory seizures and neurologic deterioration. The prognosis of PME is poor, so early diagnosis of PME is critical. The aim of our study is to identify the novel pathogenic gene in a Chinese family with PME, which may be helpful in future. A three-generation consanguineous Chinese Han family with PME was recruited. A novel homozygous variant was identified by the genetic technique of exome sequencing and certificated by Sanger sequencing and functional prediction. A novel homozygous variant, c.6975_6976insCAG, in the CACNA1A was identified in the PME family. The novel variant encoding the alpha-1A subunit of the calcium channel Cav2.1 was found in two siblings in the Chinese family and was absent in 50 normal controls. Our research indicates that the homozygous c.6975_6976insCAG might be the pathogenic mutation for PME. As a molecular diagnostic strategy, our research explores the mutation gene spectrum of PME and has resulted in significant predictions for genetic counseling.